Saturday, February 9, 2013

Life in the superorganism known as ... you

Ryan Baker-Branstetter

They say that there are certain things that you can't
unlearn. When I tell you just how many
bacteria inhabit the human body, you may find out what I'm talking about. But not to fear. Many of these commensal bacteria have
benefits to both us and the bacteria. Most
people have heard about the wide variety of microscopic organisms that have creative
and awful ways to kill us, but usually the beneficial microbes are swept under
the proverbial rug and not given their turn in the microscope spotlight. While Matteo Vaiente’s delightful blog
focused on the role of commensal bacteria and their role in digestion, we’re
going to focus on some of the other influences, specifically on how they help
the human body defend against pathogens.

First off, let's talk about these "commensal"
bacteria, as they are commonly referred to.
Commensalism is a term used to describe a relationship between two
species in which one organism benefits without affecting the other. In terms of this relationship, a much more
appropriate term would be mutualism, in which both organisms benefit. However, the industry standard is “commensal
bacteria” and much of the functions of these bacteria are unknown, so we’ll use
this as a blanket term for the bacteria that we peacefully coexist with.

It’s a fair question to ask just how “us” we actually are,
considering that commensal bacteria outnumber our own cells by about 10
times. The greatest numbers of these
bacteria are found in the digestive tract, but they are also found in the
mouth, respiratory tract, skin, and reproductive organs. They have been shown to interact with host
metabolism, produce nutrients usable by human cells, and facilitate immune
system development.

Protection against pathogenic bacteria is an important
role of the commensals living inside us.
Physically preventing adhesion and nutrient acquisition at the mucus
layer is one of the first lines of defense that commensals provide. Another defense mechanism is to produce
bacteriocidal compounds such as short-chain fatty acids, including those produced
by Lactobacilllus species commonly found in yogurt. They also serve an important role is
development of certain immune cells. Studies
have been performed using mice that lack commensal bacteria, and they have
shown increased susceptibility to bacterial, viral, and parasitic infections.

Yogurt as most people know it...

And a bit closer look (400X).

Given the important role of pathogen defense, there has
been a focus recently to manipulate intestinal flora to more efficiently
protect against invaders. One of the
most interesting studies utilized the quorum sensing system found in Vibrio cholerae, the causative agent of
Cholera. Quorum sensing is a mechanism
for bacteria to communicate with each other using small molecules called
autoinducers, which are explored in more detailed in Michael Wade’s fascinating
blog. When V. cholera concentration increases, certain autoinducers reach a level
that decreases the expression of factors that facilitate greater
pathogenesis. Mice treated with E. coli engineered to produce this
molecule showed significantly resistance to colonization by V. cholerae, Utilization of the quorum
sensing response was also used to combat Pseudomonas
aeruginosa infection. E. coli
that sensed P. aeruginosa using a quorum-sensing
system subsequently released chemicals that inhibited growth and biofilm
formation.

Commensal bacteria engineering is definitely a promising
approach to enhance human health in the future, but certain complications need
to be addressed while developing this technology. First, an effective system of delivery needs
to be developed that will allow colonization in the correct location with
damaging the bacteria or the host.
Another issue is control over colonization, maintaining a concentration
high enough to be effective, while preventing overcolonization. From a more long-term perspective, effect on
pathogenic genomes from these preventative measures would have to be assessed,
including development of resistance.

Commensal bacteria play an amazing role in our
lives. They have long been in the
shadows while outnumbering our own cells and playing critical roles in immune
system development and nutrition. Over
70% of the bacteria that reside in our guts have never even been cultured
outside the human body. There is much
more to be discovered about the superorganism that we consider to be “us”.